The cell invests significant amounts of resources to ensure that the flow of genetic information from DNA to RNA to protein is appropriately monitored and regulated. Noxious chemical, physical, or biological stressors induce cells to initiate signaling pathways for their survival or death. To mount an appropriate response, cells need to inhibit protein synthesis by sequestering messenger RNAs, activating innate immune signaling pathways, and transcriptionally upregulating stress-specific genes. The process by which messenger RNAs undergo maturation, export, stability, and translation is collectively defined as post-transcriptional gene regulation and is facilitated by RNA-binding proteins (RBPs). In addition, cytosolic RNA- and DNA-binding proteins can sense foreign or aberrantly localized nucleic acids. Hence, nucleic acid binding proteins are integral players in the cellular stress response. On one hand, RBPs coordinate gene expression through their respective functions on RNA. And on the other hand, nucleic acid sensors detect specific stressors to induce innate immune pathways into mounting a robust response. Genetic alterations within nucleic acid binding proteins can result in a wide range of diseases, including cancers, degenerative disorders, and autoimmune diseases.

The Ascano laboratory is broadly interested in two areas of cellular stress:

The roles and coordination of RNA-binding proteins in regulating gene expression during cellular stress.

and

The cytosolic DNA-sensing pathway involving the sensor cGAS, its second messenger product cGAMP, and the endoplasmic reticulum-bound receptor STING.

Our lab integrates novel biochemical, molecular and cell biological tools with high-throughput transcriptomic and proteomic technologies in an effort to elucidate the gene regulatory networks at play during cellular stress – and how such mechanisms might be manipulated for therapeutic intervention. The lab is affiliated with the Department of Biochemistry at the Vanderbilt University School of Medicine and is also part of the Immunology and Microbial Pathogenesis Programs within the Department of Pathology, Microbiology, and Immunology at VUMC.